engleski

Hypocaloric, but Not Isocaloric, Low Fat Diets Improve Microvascular Nitric Oxide Dependent Vasodilation in Obese Subjects

Introduction: Obesity is associated with microvascular dysfunction and reduced nitric oxide (NO). While low fat diets improve cardiovascular risk, the contributions of macronutrients, independent of weight loss (WL) on microvascular function is not known. We tested the hypothesis that NO-dependent, vasodilator function in microvessels is improved by low fat diets designed for weight loss (LFWL) compared to low fat weight maintenance (LFWM). Methods: Obese adults (BMI= 34 + 4 kg/m2) were randomly assigned to either an energy-restricted LFWL diet (n=11, 500 calorie/day deficit) or an isocaloric LFWM diet designed to maintain weight (n=10). All meals were prepared and delivered for 6 weeks and were modeled after the AHA LF diet (50% CHO ; 30% protein ; 20% fat). Microvessels (internal diameter, 133±38 μm) were obtained from gluteal subcutaneous fat pad biopsies at weeks 1 (pre) and 6 (post) for vascular reactivity measurements to acetylcholine (ACh ; 10-9-10-4 M), and flow (pressure gradients: {; ; Delta}; ; 10- {; ; Delta}; ; 100 cmH2O), with and without L-NAME (10-4 M, NOS inhibitor) or Indomethacin (INDO, 10-5 M, cyclooxygenase inhibitor). Vascular NO was measured by fluorescence microscopy. Results: LFWL diet reduced BMI (29.3 + 2.0, p<0.05 vs. pre 32.6 + 2.5 kg/m2), and increased flow- induced vasodilation (FID ; {; ; Delta}; ; 100 cmH2O: 86 + 4%, p<0.01 vs. pre 69 + 2%) and ACh-induced vasodilation (AChID) in post (Max: 85 + 5, p<0.05 vs. pre 73 + 6). NOS inhibition reduced FID and AChID (p<0.05). The increased NO fluorescence after 6 weeks of LFWL (fluorescence ratio: 1.2, post vs. pre, p<0.001) was inhibited by L-NAME (0.75, p<0.01). Conversely, LFWM diet had no effect on BMI, FID or AChID pre vs. post diet. There was no effect of LFWM on NO compared to pre diet. INDO reduced maximum FID and AChID in pre (p<0.05) and there was no effect of either diet on this reduction in post. Conclusion: We found that 1) low fat diets designed for WL improve microvascular reactivity compared to similar diets not designed for WL and 2) increased vascular NO contributes to the improved microvascular dilation to flow and ACh after 6 weeks of WL on low fat diet. These data suggest that weight reduction (and not the associated changes in macronutrient content) on low fat diet is critical for improved microvascular function.

Nitric oxide; Endothelium; Diet; Obesity; Peripheral vasculature

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